Abstracts Category : Other

Identifying Novel Molecular Biomarkers and Therapeutic Targets for Prostate Cancer

by Tanushree Shenoy

Prostate cancer is the most common malignancy in males, and the third leading cause of male cancer-related death in the Western world. Although most prostate cancers are diagnosed at an early and treatable stages, predicting the outcome of prostate cancer progression and treatment has proven to be challenging because of the heterogeneous nature of the disease. Recent cancer genome studies have identified novel alterations as well as the potential actionable targets. Among these novel alterations is chromodomain helicase DNA-binding protein 1 (CHD1). CHD1 deletion occurs in as many as 20% of prostate cancers and may be associated with genomic instability. To validate the function of CHD1 in prostate cancer in vivo, we created the Pb-Cre+;Chd1L/L mouse model, whereby Chd1 is deleted in mouse prostate epithelial cells, and engineered CHD1-deleted prostate cancer cell lines. We found that while Chd1 deletion alone does not induce prostate cancer in vivo, it confers DNA damage sensitivity and homologous recombination impairment, making CHD1-deficient cells sensitive to PARP inhibitors and Platinum-based drugs. A metastatic castrate-resistant prostate cancer patient whose tumors had CHD1 deletion was responsive to carboplatin, suggesting that CHD1 status may be a biomarker for PARP inhibitor and platinum treatment responsiveness.